Influence of aversive stimulation on haloperidol-induced catalepsy in rats Nayara C.B. Barroca a,b , Mariana D. Guarda c , Naiara T. da Silva c , Ana C. Colombo a,b , Adriano E. Reimer a,b , Marcus L. Brandão a,b and Amanda R. de Oliveira a,b,c Catalepsy – an immobile state in which individuals fail to change imposed postures – can be induced by haloperidol. In rats, the pattern of haloperidol-induced catalepsy is very similar to that observed in Parkinson’s disease (PD). As some PD symptoms seem to depend on the patient’s emotional state, and as anxiety disorders are common in PD, it is possible that the central mechanisms regulating emotional and cataleptic states interplay. Previously, we showed that haloperidol impaired contextual-induced alarm calls in rats, without affecting footshock-evoked calls. Here, we evaluated the influence of distinct aversive stimulations on the haloperidol-induced catalepsy. First, male Wistar rats were subjected to catalepsy tests to establish a baseline state after haloperidol or saline administration. Next, distinct cohorts were exposed to open-field; elevated plus- maze; open-arm confinement; inescapable footshocks; contextual conditioned fear; or corticosterone administration. Subsequently, catalepsy tests were performed again. Haloperidol-induced catalepsy was verified in all drug-treated animals. Exposure to open-field, elevated plus-maze, open-arm confinement, footshocks, or administration of corticosterone had no significant effect on haloperidol-induced catalepsy. Contextual conditioned fear, which is supposed to promote a more intense fear, increased catalepsy over time. Our findings suggest that only specific defensive circuitries modulate the nigrostriatal system mediating the haloperidol-induced cataleptic state. Behavioural Pharmacology 30:229–238 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Behavioural Pharmacology 2019, 30:229–238 Keywords: catalepsy, dopamine, fear/anxiety, haloperidol, Parkinson’s disease, rat, stress a Institute of Neuroscience and Behavior (INeC), b Department of Psychology, University of São Paulo (USP), Ribeirão Preto and c Department of Psychology, Federal University of São Carlos (UFSCar), São Carlos, Sao Paulo, Brazil Correspondence to Amanda R. de Oliveira, PhD, Department of Psychology, Federal University of São Carlos (UFSCar), km 235 Washington Luís Rd, 13565- 905 São Carlos, Sao Paulo, Brazil E-mail: aroliveira@ufscar.br Received 14 May 2018 Accepted as revised 28 November 2018 Introduction Antipsychotics are drugs that are used clinically in the treat- ment of schizophrenic symptoms that act by altering dopa- minergic receptor signaling (Creese et al. , 1976; Reynolds, 1992). Besides the clinical effects, some antipsychotic drugs can induce unwanted extrapyramidal side effects such as parkinsonism, akathisia, and acute dystonia by blocking striatal dopaminergic D2 receptors (Reynolds, 1992; Kane and Freeman, 1994; Wadenberg et al. , 2001; Porsolt et al. , 2013). In rodents, haloperidol – one of the most widely used anti- psychotics – can induce catalepsy, a state of bradykinesia and rigidity in which individuals fail to correct externally imposed postures (De Ryck et al. , 1980; Sanberg, 1980; Wadenberg et al. , 2001; Vasconcelos et al. , 2003). Drug-induced catalepsy in rodents has been used to determine differences in potency and extrapyramidal effects of putative antipsychotics during the drug discovery phase (Sanberg et al. , 1988; Lorenc-Koci et al. , 1996; Wadenberg et al. , 2001). This drug-induced cataleptic state also provides a simple and useful animal model for investigating the motor impairments often observed in Parkinson’ s disease (PD) and the antiparkinsonian potential of drugs (Sanberg et al. , 1988; Lorenc-Koci et al. , 1996; Trevitt et al. , 2009; Greco et al. , 2010; Duty and Jenner, 2011; Ionov and Severtsev, 2012). PD is a progressive neurodegenerative disorder manifested by a broad spectrum of motor and nonmotor symptoms. Tremor at rest, rigidity, postural instability, and bradykinesia are the most common motor symptoms (Parkinson, 2002; Jankovic, 2008b; Broen et al. , 2016). Some motor symptoms of PD may be dependent on the emotional state of the patient. For example, paralyzed patients can react and make quick movements in externally driven or urgent situations. This phenomenon, called paradoxical kinesia, suggests that despite having a relatively intact motor function, PD patients present difficulties in accessing motor programs without an external trigger, such as a loud noise or an important visual cue (Flowers, 1978; Bloxham et al., 1984; Glickstein and Stein, 1991; Jankovic, 2008b; Melo-Thomas and Thomas, 2015). Nonmotor symptoms are also common in PD. Although aspects related to disturbed emotional processing in PD patients have attracted more attention in recent years (Moonen et al., 2017), it is still an under-appreciated feature Research report 229 0955-8810 Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. DOI: 10.1097/FBP.0000000000000462 Copyright r 2019 Wolters Kluwer Health, Inc. All rights reserved.